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Administrative data

Description of key information

LD50 Oral mice  > 5000 mg/Kg bw
LD50 Oral Inhalatory rat > 13800 mg/m3

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1971
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Secondary source
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
not specified
Sex:
not specified
Route of administration:
oral: unspecified
Vehicle:
not specified
Doses:
5.0, 12.5, 25.0, 50.0 ml/kg
No. of animals per sex per dose:
groups with 5, 5, 10 and 10 mice
Control animals:
not specified
Sex:
male/female
Dose descriptor:
LD0
Effect level:
ca. 50 mL/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 50 mL/kg bw
Based on:
test mat.
Mortality:
no mortality observed
Clinical signs:
no clinical signs observed
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In the seven-day observation period, no toxic effects were observed and no deaths occurred. The single dose oral LD50 was determined to be greater than 50 ml/kg in mice.
Executive summary:

Squalene has been tested for acute oral toxicity on mice. The single dose oral LD50 was determined to be greater than 50 ml/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
50 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Secondary source
Qualifier:
according to
Guideline:
other: Federal Hazardous Substances Act (FHSA
Deviations:
not specified
GLP compliance:
no
Test type:
fixed concentration procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Strain: Sherman
Route of administration:
other: spray formulation
Type of inhalation exposure:
whole body
Vehicle:
not specified
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
ca. 1 h
Concentrations:
345 mg/L
No. of animals per sex per dose:
5 x sex x dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:no data
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LC0
Effect level:
ca. 9.1 other: mg/kg
Based on:
test mat.
Exp. duration:
1 h
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Autopsy 14 days after exposure revealed no abnormalities. LC0= 9.1 mg/kg bw
Executive summary:

The similar substance has been tested for acute inhalation toxicity on rats. The acute dose of 9.1 mg/kg doesen't show any abnormalities.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
13 800 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Two old studies are reported in a CIR review indicating no effect for acute oral toxicity at very high doses (CTFA 1971, 1972). Further information on acute toxicity can be found in Yamaguchi T. (Yamaguchi T,Nakagawa M,Hidaka K,Yoshida T,Sasaki T,Akiyama S,Kuwano M.Potentiation by squalene of antitumor effect of 3-[(4-amino-2-methyl-5-pyrimidinyl)methyl]-1-(2-chloroethyl)-nitros ourea in a murine tumor system.Jpn J Cancer Res.1985 Oct;76(10):1021-6.), where a dose of 5000 mg/Kg bw has been reported in the framework of investigaton of squalene as antitumoral agent.

Squalene has also been extensively tested for subcutaneous and muscular application, due to his application as a antiinfluenzal vaccin H1N1 with no effect.

Inhalatory exposure to the parent compound squalane indicate no indication of acute toxicity up to the level of 13.8 mg/l

In conclusion, no concern for acute toxicity is arisen from Squalene


Justification for selection of acute toxicity – oral endpoint
The study seems performed on the substance at highest purity

Justification for selection of acute toxicity – inhalation endpoint
This study has been performed at a slightly higher concentration that the other one

Justification for classification or non-classification

Oral acute toxicity

The substance is not classified for oral toxicity because it doesn't meet the classification criteria of the CLP regulation n. 1272/2008:

Oral (mg/kg bodyweight)

Category 1: ATE ≤ 5

Category 2: 5 < ATE≤ 50

Category 3: 50 < ATE≤ 300

Category 4: 300 < ATE≤ 2 000

Inhalation acute toxicity

The substance is not classified for inhalation acute toxicity because it doesn't meet the classification criteria of the CLP regulation n. 1272/2008:

Vapours (mg/l)

Category 1: ATE ≤ 0,5

Category 2: 0,5 < ATE ≤ 2,0

Category 3: 2,0 < ATE ≤ 10,0

Category 4: 10,0 < ATE ≤ 20,0

Test result for inhalatory is setting a no effect concentration of 13.7 mg/l. It can be estimated that LD50 will be greater than 20 mg/l

Nevertheless, according to CLP criteria, a classification for aspiration hazard has to be considered, since squalene is a hydrocarbon:

Category Criteria

Category 1

Substances known to cause human aspiration toxicity hazards or to be regarded as if they cause human aspiration toxicity hazard

A substance is classified in Category 1:

(a) based on reliable and good quality human evidence or

(b) if it is a hydrocarbon and has a kinematic viscosity of 20,5 mm2/s or less, measured at 40 oC.

Kinematic viscosity of squalene has been measured on several samples and resulted always < than 20 mm2/s

Incidences of lipoid pneumonia have been reported for several mineral and animal oils, where the presence of fatty acids seems to increase the incidence of pneumonia as mentioned in a study by Asnis, Saltzman, & Melchert (1993).

The same authors describe a case of exogenous lipoid pneumonia after excessive intake of squalene capsules in a Korean patient. Meltzer et al, (2006) concluded in their study that lipoid pneumonia occurs prevalently in elderly patients and in patients, predisposed with for instance gastroesophageal reflux and that the majority of cases of LP in western countries appear to be iatrogenic, while squalene as a source of LP is reported in Far East countries due to its medicinal use in that region

Even if the classification is proposed it has to be taken into account that squalene has been ingested by humans as a component of shark/fish liver oil for centuries as food supplements, and as a component of olive and other oils, without exhibiting aspiration toxicity under normal use.

As a conclusion, in a precautionary approach, squalene is proposed for haspiration hazaard classification